Neuroscience

Proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus are essential to regulate food intake and energy balance. However, the ontogenetic transcriptional programs that specify the identity and functioning of these neurons are poorly understood. Here, we use single-cell RNA-sequencing (scRNA-seq) to define the transcriptomes characterizing Pomc-expressing cells in the developing hypothalamus and translating ribosome affinity purification with RNA-sequencing (TRAP-seq) to analyze the subsequent translatomes of mature POMC neurons.

Dyslipidemia and autophagy have been implicated in the pathogenesis of blinding neovascular age-related macular degeneration (NV-AMD). Very low-density lipoprotein receptor (VLDLR), expressed in photoreceptors with a high metabolic rate, facilitates the uptake of triglyceride-derived fatty acids (FA). Since FA uptake is reduced in Vldlr-/- tissues, more remain in circulation, and the retina is fuel deficient, driving the formation in mice of neovascular lesions reminiscent of retinal angiomatous proliferation (RAP), a subtype of NV-AMD.

The neuropathological background of major depression and anxiety as non-motor symptoms of Parkinson's disease is much less understood than classical motor symptoms. Although, neurodegeneration of the Edinger-Westphal nucleus in human Parkinson's disease is a known phenomenon, its possible significance in mood status has never been elucidated.

Retinal gene therapy using RNA interference (RNAi) to silence targeted genes requires both efficacy and safety. Short hairpin RNAs (shRNAs) are useful for RNAi, but high expression levels and activity from the co-delivered passenger strand may cause undesirable cellular responses. Ago2-dependent shRNAs (agshRNAs) produce no passenger strand activity.

Traumatic brain injury (TBI) and spinal cord injury (SCI) are two main central nervous system (CNS) traumas, caused by external physical insults. Both injuries have devastating effects on the quality of life, and there is no effective therapy at present. Notably, gene expression profiling using bulk RNA sequencing (RNA-Seq) and single-cell RNA-Seq (scRNA-Seq) have revealed significant changes in many coding and non-coding genes, as well as important pathways in SCI and TBI.

Satellite glia are the major glial type found in sympathetic and sensory ganglia in the peripheral nervous system, and specifically, contact neuronal cell bodies. Sympathetic and sensory neurons differ in morphological, molecular, and electrophysiological properties. However, the molecular diversity of the associated satellite glial cells remains unclear. Here, using single-cell RNA sequencing analysis, we identify five different populations of satellite glia from sympathetic and sensory ganglia.

Neuron-glia interactions play a critical role in the regulation of synapse formation and circuit assembly. Here we demonstrate that canonical Sonic hedgehog (Shh) pathway signaling in cortical astrocytes acts to coordinate layer-specific synaptic connectivity. We show that the Shh receptor Ptch1 is expressed by cortical astrocytes during development and that Shh signaling is necessary and sufficient to promote the expression of genes involved in regulating synaptic development and layer-enriched astrocyte molecular identity.

The subthalamic nucleus (STN) controls psychomotor activity and is an efficient therapeutic deep brain stimulation target in individuals with Parkinson's disease. Despite evidence indicating position-dependent therapeutic effects and distinct functions within the STN, the input circuit and cellular profile in the STN remain largely unclear. Using neuroanatomical techniques, we construct a comprehensive connectivity map of the indirect and hyperdirect pathways in the mouse STN.

Spinal cord ependymal cells display neural stem cell properties in vitro and generate scar-forming astrocytes and remyelinating oligodendrocytes after injury. We report that ependymal cells are functionally heterogeneous and identify a small subpopulation (8% of ependymal cells and 0.1% of all cells in a spinal cord segment), which we denote ependymal A (EpA) cells, that accounts for the in vitro stem cell potential in the adult spinal cord. After spinal cord injury, EpA cells undergo self-renewing cell division as they give rise to differentiated progeny.

Background Substance use disorders (SUDs) are associated with disruptions in circadian rhythms. Both human and animal work has shown the integral role for circadian clocks in the modulation of reward behaviors. Interestingly, astrocytes have emerged as key regulators of circadian rhythmicity. However, no studies to date have identified the role of circadian astrocyte function in the nucleus accumbens (NAc), a hub for reward regulation, or determined the importance of these rhythms for reward-related behavior.